Merck

ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.

iScience (2021-08-07)
Takashi Sugiyama, Naoya Murao, Hisae Kadowaki, Keizo Takao, Tsuyoshi Miyakawa, Yosuke Matsushita, Toyomasa Katagiri, Akira Futatsugi, Yohei Shinmyo, Hiroshi Kawasaki, Juro Sakai, Kazutaka Shiomi, Masamitsu Nakazato, Kohsuke Takeda, Katsuhiko Mikoshiba, Hidde L Ploegh, Hidenori Ichijo, Hideki Nishitoh
RESUMEN

Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of Derlin-1 or Derlin-2 in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits. Derlin-1 or Derlin-2 deficiency reduced neurite outgrowth in vitro and in vivo and surprisingly also inhibited sterol regulatory element binding protein 2 (SREBP-2)-mediated brain cholesterol biosynthesis. In addition, reduced neurite outgrowth due to Derlin-1 deficiency was rescued by SREBP-2 pathway activation. Overall, our findings demonstrate that Derlins sustain brain cholesterol biosynthesis, which is essential for appropriate postnatal brain development and function.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Deoxyribonuclease I from bovine pancreas, Type II, lyophilized powder, Protein ≥80 %, ≥2,000 units/mg protein
Sigma-Aldrich
Monoclonal Anti-MAP2 antibody produced in mouse, clone HM-2, ascites fluid
Sigma-Aldrich
Cytosine β-D-arabinofuranoside, crystalline, ≥90% (HPLC)
Sigma-Aldrich
SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, sterile-filtered, aqueous solution, suitable for cell culture
Sigma-Aldrich
Monoclonal Anti-Calbindin-D-28K antibody produced in mouse, clone CB-955, ascites fluid
Sigma-Aldrich
Monoclonal Anti-Actin antibody produced in mouse, clone AC-40, ascites fluid
Sigma-Aldrich
Papain from papaya latex, buffered aqueous suspension, 2× Crystallized, ≥16 units/mg protein
Sigma-Aldrich
Poly-L-lysine hydrobromide, mol wt 30,000-70,000
Sigma-Aldrich
Monoclonal Anti-S-100 (β-Subunit) antibody produced in mouse, clone SH-B1, ascites fluid
Sigma-Aldrich
25-Hydroxycholesterol, ≥98%